Monitoramento terapêutico do ácido micofenólico: validação de método e análise de interação com omeprazol

Abstract

Renal transplantation has been deemed the best treatment for patients with end stage renal disease. Mycophenolic acid is an immunosuppressant widely used in transplantation, acting as a potent, selective, non-competitive and reversible inhibitor of inosine monophosphate-dehydrogenase enzyme. Currently, two compounds are available: mycophenolate mofetil and mycophenolate sodium, both presenting with high rate of gastrointestinal complications. In clinical practice, patients are routinely prescribed with fixed doses, which can lead to drug exposure differences as great as 10 times. Therapeutic monitoring of Mycophenolic acid appears as a helping tool, useful for adjusting doses, individualizing therapy and promoting better understanding of drug interactions on the pharmacokinetics of Mycophenolic acid. Omeprazole is a widely prescribed drugs for transplanted patient, either as prophylaxis of gastric disorders or peptic ulcers therapy. However, literature data have hinted at a possible omeprazole interaction on Mycophenolic acid pharmacokinetics, by raising gastric pH and reducing its gastric absorption. The aim of the current study was to evaluate Mycophenolic acid levels in patients using mycophenolate mofetil or mycophenolate sodium with and without co-administration of omeprazole. The method for therapeutic drug monitoring of Mycophenolic acid seemed consistent with previously established validation parameters. There was no statistical difference in Mycophenolic acid levels of patients using either mycophenolate mofetil or mycophenolate sodium, with or without concomitant omeprazole; yet Mycophenolic acid plasma levels presented lower variance when omeprazole was concomitantly used, in both groups.